Zhao Li , Marius Thomas , Christian M. Berač , Oliver S. Stach , Pol Besenius , John B. Matson
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引用次数: 0
Abstract
Self-assembled peptides provide a modular and diverse platform for drug delivery, and innovative delivery methods are needed for delivery of hydrogen sulfide (H2S), an endogenous signaling molecule (gasotransmitter) with significant therapeutic potential. Of the available types of H2S donors, peptide/protein H2S donor conjugates (PHDCs) offer significant versatility. Here we discuss the design, synthesis, and in-depth study of a PHDC containing three covalently linked components: a thiol-triggered H2S donor based on an S-aroylthiooxime (SATO), a GFFF tetrapeptide, and a tetraethylene glycol (TEG) dendron. Conventional transmission electron microscopy showed that the PHDC self-assembled into spherical structures without heat or stirring, but it formed nanofibers with gentle heat (37 °C) and stirring. Circular dichroism (CD) spectroscopy data collected during self-assembly under nanofiber-forming conditions suggested an increase in β-sheet character and a decrease in organization of the SATO units. Release of H2S from the nanofibers was studied through triggering with various thiols. The release rate and total amount of H2S released over both short (5 h) and long (7 d) time scales varied with the charge state: negatively charged and zwitterionic thiols (e.g., Ac-Cys-OH and H-Cys-OH) triggered release slowly while a neutral thiol (Ac-Cys-OMe) showed ∼10-fold faster release, and a positively charged thiol (H-Cys-OMe) triggered H2S release nearly 50-fold faster than the negatively charged thiols. CD spectroscopy studies monitoring changes in secondary structure over time during H2S release showed similar trends. This study sheds light on the driving forces behind self-assembling nanostructures and offers insights into tuning H2S release through thiol charge state modulation.
期刊介绍:
Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.